The overall aim is to define the mechanisms of immune injury to the lungs in occupationally related pulmonary diseases. Using an experimental model in rabbits which is monitored by changes in areterial blood gases, attempts are being made to produce the disease hypersensitivity pneumontitis. Animals are immunized via the aerosol route with classical protein antigens or fungal spores known to produce spontaneous human disease. These animals are then aerosol challenged and the following data obtained at timed intervals thereafter: arterial PaO2, CH50 titer, and quantitative precipitin production. Further studies also include the study of cell mediated reactivity of these animals to the antigen in question. In this manner, the validity of claims on the mechanism of pathogenesis of this disease can be examined, e.g., Type II, III, IV, Mixed, or complement activation. Also being studied, in diseases of the pulmonary system other than hypersensitivity pneumonitis, is the development of cell mediated reactivity to autologous lung connective tissue antigens. Such reactivity has been shown to develop in a variety of experimental animal diseases and spontaneously in a limited number of humans with chronic pulmonary disease. A survey of the extent of such human reactivity is being planned as is a study on the pathologic effect of such reactivity.